Table of Contents

Research Articles

• Research Articles

  The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment

  Juha P. Väyrynen, Koichiro Haruki, Mai Chan Lau, Sara A. Väyrynen, Rong Zhong, Andressa Dias Costa, Jennifer Borowsky, Melissa Zhao, Kenji Fujiyoshi, Kota Arima, Tyler S. Twombly, Junko Kishikawa, Simeng Gu, Saina Aminmozaffari, Shanshan Shi, Yoshifumi Baba, Naohiko Akimoto, Tomotaka Ugai, Annacarolina Da Silva, Jennifer L. Guerriero, Mingyang Song, Kana Wu, Andrew T. Chan, Reiko Nishihara, Charles S. Fuchs, Jeffrey A. Meyerhardt, Marios Giannakis, Shuji Ogino and Jonathan A. Nowak

  Cancer Immunol Res January 1 2021 9 (1) 8-19; DOI:10.1158/2326-6066.CIR-20-0527

  
  

  Macrophage polarization state, rather than overall density, in the colorectal cancer microenvironment is associated with cancer-specific survival independent of potential confounding factors, with M1-like and M2-like macrophage phenotypes exhibiting distinct prognostic roles.
• Research Articles

  Retinoic Acid Synthesis Deficiency Fosters the Generation of Polymorphonuclear Myeloid-Derived Suppressor Cells in Colorectal Cancer

  Hong-Wei Sun, Jing Chen, Wen-Chao Wu, Yan-Yan Yang, Yi-Tuo Xu, Xing-Juan Yu, Hai-Tian Chen, Zilian Wang, Xiao-Jun Wu and Limin Zheng

  Cancer Immunol Res January 1 2021 9 (1) 20-33; DOI:10.1158/2326-6066.CIR-20-0389

  
  

  A defect in ADH1-mediated retinoic acid synthesis contributes to the accumulation of polymorphonuclear (PMN)-MDSCs in colorectal cancer. The data highlight how restoring retinoic acid signaling could abrogate the generation of PMN-MDSCs and improve antitumor responses.
• Research Articles | AuthorChoice

  A CRISPR Screen Reveals Resistance Mechanisms to CD3-Bispecific Antibody Therapy

  Si-Qi Liu, Alyssa Grantham, Casey Landry, Brian Granda, Rajiv Chopra, Srinivas Chakravarthy, Sabine Deutsch, Markus Vogel, Katie Russo, Katherine Seiss, William R. Tschantz, Tomas Rejtar, David A. Ruddy, Tiancen Hu, Kimberly Aardalen, Joel P. Wagner, Glenn Dranoff and Joseph A. D'Alessio

  Cancer Immunol Res January 1 2021 9 (1) 34-49; DOI:10.1158/2326-6066.CIR-20-0080

  
  

  A genome-wide CRISPR screen was developed to understand cancer cell–derived resistance mechanisms to CD3-bispecific antibodies. The screen identifies IFNγ signaling being pivotal for responsiveness to CD3 bispecifics, and deficiency in core fucosylation as causing resistance to the therapeutic flotetuzumab.
• Research Articles

  A Bispecific Antibody Antagonizes Prosurvival CD40 Signaling and Promotes Vγ9Vδ2 T cell–Mediated Antitumor Responses in Human B-cell Malignancies

  Iris de Weerdt, Roeland Lameris, George L. Scheffer, Jana Vree, Renate de Boer, Anita G. Stam, Rieneke van de Ven, Mark-David Levin, Steven T. Pals, Rob C. Roovers, Paul W.H.I. Parren, Tanja D. de Gruijl, Arnon P. Kater and Hans J. van der Vliet

  Cancer Immunol Res January 1 2021 9 (1) 50-61; DOI:10.1158/2326-6066.CIR-20-0138

  
  

  The generation of a CD40-specific Vγ9Vδ2 T-cell engager, which abrogates prosurvival CD40 signaling, is described. This bispecific antibody unleashes Vγ9Vδ2 T cell–mediated responses against both leukemia and multiple myeloma in vitro and in vivo.
• Research Articles | AuthorChoice

  CD28 Costimulatory Domain–Targeted Mutations Enhance Chimeric Antigen Receptor T-cell Function

  Justin C. Boucher, Gongbo Li, Hiroshi Kotani, Maria L. Cabral, Dylan Morrissey, Sae Bom Lee, Kristen Spitler, Nolan J. Beatty, Estelle V. Cervantes, Bishwas Shrestha, Bin Yu, Aslamuzzaman Kazi, Xuefeng Wang, Said M. Sebti and Marco L. Davila

  Cancer Immunol Res January 1 2021 9 (1) 62-74; DOI:10.1158/2326-6066.CIR-20-0253

  
  

  CD28 mutations enhance CAR T-cell function by reducing expression of transcription factors such as NFAT and NUR77, which in turn reduce expression of exhaustion-related genes. These data highlight considerations for CAR design that could improve antitumor responses.
• Research Articles | AuthorChoice

  The Cerebroventricular Environment Modifies CAR T Cells for Potent Activity against Both Central Nervous System and Systemic Lymphoma

  Xiuli Wang, Christian Huynh, Ryan Urak, Lihong Weng, Miriam Walter, Laura Lim, Vibhuti Vyas, Wen-Chung Chang, Brenda Aguilar, Alfonso Brito, Aniee Sarkissian, N. Achini Bandara, Lu Yang, Jinhui Wang, Xiwei Wu, Jianying Zhang, Saul J. Priceman, Hong Qin, Larry W. Kwak, Lihua E. Budde, Sandra H. Thomas, Mary C. Clark, Leslie Popplewell, Tanya Siddiqi, Christine E. Brown and Stephen J. Forman

  Cancer Immunol Res January 1 2021 9 (1) 75-88; DOI:10.1158/2326-6066.CIR-20-0236

  
  

  In the clinic, CD19-CAR T cells are administered IV and are not used specifically to treat CNS lymphoma. The authors show a single ICV infusion of CD19-CAR T cells completely eradicates both CNS and systemic lymphoma in mice.
• Research Articles

  Activin A Promotes Regulatory T-cell–Mediated Immunosuppression in Irradiated Breast Cancer

  Mara De Martino, Camille Daviaud, Julie M. Diamond, Jeffrey Kraynak, Amandine Alard, Silvia C. Formenti, Lance D. Miller, Sandra Demaria and Claire Vanpouille-Box

  Cancer Immunol Res January 1 2021 9 (1) 89-102; DOI:10.1158/2326-6066.CIR-19-0305

  
  

  Activin A and TGFβ can shape the breast cancer tumor microenvironment after radiotherapy. Dual blockade of activin A and TGFβ reverses radiotherapy-induced Treg increases and boosts antitumor responses, highlighting potential targetable factors for breast cancer treatment.
• Research Articles

  Improved T-cell Receptor Diversity Estimates Associate with Survival and Response to Anti–PD-1 Therapy

  Dante S. Bortone, Mark G. Woodcock, Joel S. Parker and Benjamin G. Vincent

  Cancer Immunol Res January 1 2021 9 (1) 103-112; DOI:10.1158/2326-6066.CIR-20-0398

  
  

  Inaccurate TCR diversity estimates from RNA sequencing data have made the relationship between diversity and immunotherapy responses unclear. Improved estimation of diversity uncovers the association between diversity and responses of melanoma patients treated with PD-1 inhibition.
• Research Articles

  Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer

  Wen-Der Lin, Tan-Chi Fan, Jung‐Tung Hung, Hui-Ling Yeo, Sheng-Hung Wang, Chu-Wei Kuo, Kay-Hooi Khoo, Li-Mei Pai, John Yu and Alice L. Yu

  Cancer Immunol Res January 1 2021 9 (1) 113-122; DOI:10.1158/2326-6066.CIR-20-0203

  
  

  Silencing of the ST3GAL1 glycosyltransferase in breast cancer cells reduces O-sialylation of CD55, enhancing C3 deposition and susceptibility to complement- and antibody-dependent cytotoxicity. These findings suggest ST3GAL1 inhibition could be a strategy to block breast cancer immune evasion.